Multi-target design of fused cyclic pyrimidine-2-thione candidates as DNA intercalators and topoisomerase I/II inhibitors.
1/5 보강
[AIM] We aimed to design and synthesize novel pyrimidine-2-thione derivatives (-) as Topoisomerase I/II (Topo I/II) inhibitors with DNA intercalation potential for cancer treatment.
APA
Khalil MS, Al-Karmalawy AA, et al. (2026). Multi-target design of fused cyclic pyrimidine-2-thione candidates as DNA intercalators and topoisomerase I/II inhibitors.. Future medicinal chemistry, 18(1), 35-48. https://doi.org/10.1080/17568919.2025.2602424
MLA
Khalil MS, et al.. "Multi-target design of fused cyclic pyrimidine-2-thione candidates as DNA intercalators and topoisomerase I/II inhibitors.." Future medicinal chemistry, vol. 18, no. 1, 2026, pp. 35-48.
PMID
41388737 ↗
Abstract 한글 요약
[AIM] We aimed to design and synthesize novel pyrimidine-2-thione derivatives (-) as Topoisomerase I/II (Topo I/II) inhibitors with DNA intercalation potential for cancer treatment.
[MATERIALS & METHODS] Inhibitory concentration 50 (IC) against mammary gland breast cancer, hepatocellular carcinoma, and colorectal carcinoma was determined for all compounds. The frontier candidates (, , , , and ) were evaluated for their DNA-binding ability, Topo I, and Topo II inhibiting potential. Moreover, cell cycle and apoptosis analysis were carried out.
[RESULTS] Compound displayed the best DNA-binding affinity with an IC value of 37.24 µM in comparison to doxorubicin (Dox). Both compounds and showed superior nanomolar Topo I inhibitory potential, compared to Dox. Similarly, compounds and achieved better Topo II inhibition, exceeding that of Dox. It was revealed that compound halted the cell cycle at both the P1 and G2 phases. In addition, compound was able to boost the apoptosis at both the early and late apoptotic phases.
[CONCLUSION] Consequently, the compounds afforded can be regarded as prominent lead anticancer compounds for further optimization and investigation.
[MATERIALS & METHODS] Inhibitory concentration 50 (IC) against mammary gland breast cancer, hepatocellular carcinoma, and colorectal carcinoma was determined for all compounds. The frontier candidates (, , , , and ) were evaluated for their DNA-binding ability, Topo I, and Topo II inhibiting potential. Moreover, cell cycle and apoptosis analysis were carried out.
[RESULTS] Compound displayed the best DNA-binding affinity with an IC value of 37.24 µM in comparison to doxorubicin (Dox). Both compounds and showed superior nanomolar Topo I inhibitory potential, compared to Dox. Similarly, compounds and achieved better Topo II inhibition, exceeding that of Dox. It was revealed that compound halted the cell cycle at both the P1 and G2 phases. In addition, compound was able to boost the apoptosis at both the early and late apoptotic phases.
[CONCLUSION] Consequently, the compounds afforded can be regarded as prominent lead anticancer compounds for further optimization and investigation.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- Topoisomerase I Inhibitors
- Topoisomerase II Inhibitors
- Pyrimidines
- Antineoplastic Agents
- Drug Design
- DNA Topoisomerases
- Type I
- Apoptosis
- Type II
- Structure-Activity Relationship
- Drug Screening Assays
- Antitumor
- Intercalating Agents
- Thiones
- DNA
- Molecular Structure
- Cell Line
- Tumor
- Cell Proliferation
- Cell Cycle
- DNA-intercalation
- Multi-target
- pyrimidine-2-thione
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